Feeding diets containing animal protein increases plasma LDL cholesterol concentrations compared to feeding diets containing plant protein. However, although the effect of animal and plant proteins on plasma cholesterol concentrations is known, the mechanism(s) by which this effect occurs is not known. The proposed research will attempt to answer some questions that exist about dietary protein effects on plasma cholesterol concentrations. The first question to be addressed in the proposed research is, when does plasma cholesterol levels change after the start of the feeding of each diet. That is, if plasma cholesterol levels change prior to a change in liver cholesterol synthesis it would indicate that a change in cholesterol synthesis rate is not responsible for the change in plasma cholesterol levels. A second objective of the proposed study is to investigate the hypothesis that dietary proteins modulate plasma cholesterol concentrations by altering thyroxine status. Previous research by the investigator has shown that feeding casein reduces plasma thyrocine levels relative to feeding soy protein. Hypothyroidism is characterized by an increased plasma total and LDL cholesterol levels (similar to changes observed when casein is fed). These experiments will investigate whether the effects of the various proteins on plasma cholesterol levels remain when thyroxine status is altered. Gerbils will be fed experimental, high fat diets, with and without added cholesterol, containing one of two sources of protein: soy protein (plant) and casein (animal). Additinally in the diets of one-half of the animals, propylthiouracil (PTU), a potent inhibitor of thyroxine will be added. Plasma lipoprotein cholesterol and plasma thyrocine hormone concentrations will be determined in these animals. Fecal sterol excretions and hepatic cholesterol synthesis will also be determined. This research will focus on interaction of dietary protein sources and thyroxine. From a mechanistic standpoint, future research investigating dietary ingredient effects on cholesterol metabolism are likely to focus on interactions with hormones.